Journal
ONCOTARGET
Volume 8, Issue 17, Pages 28544-28557Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15325
Keywords
ischemia and reperfusion; microglia; neurogenesis; sevoflurane preconditioning; stem cells
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Funding
- Science Fund of Natural Science Foundation of China [81200937, 81271259]
- Science & Technology Commission of Shanghai Municipality [14XD 1402900]
- Zhuo xue plan, Huajing plan, Huashan hospital, Fudan University
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Brain ischemia causes irreversible damage to functional neurons in cases of infarct. Promoting endogenous neurogenesis to replace necrotic neurons is a promising therapeutic strategy for ischemia patients. The neuroprotective role of sevoflurane preconditioning implies that it might also enhance endogenous neurogenesis and functional restoration in the infarct region. By using a transient middle cerebral artery occlusion (tMCAO) model, we discovered that endogenous neurogenesis was enhanced by sevoflurane preconditioning. This enhancement process is characterized by the promotion of neuroblast proliferation within the subventricular zone (SVZ), migration and differentiation into neurons, and the presence of astrocytes and oligodendrocytes at the site of infarct. The newborn neurons in the sevoflurane preconditioning group showed miniature excitatory postsynaptic currents (mEPSCs), increased synaptophysin and PSD95 staining density, indicating normal neuronal function. Furthermore, long-term behavioral improvement was observed in the sevoflurane preconditioning group consistent with endogenous neurogenesis. Further histological analyses showed that sevoflurane preconditioning accelerated microglial activation, including migration, phagocytosis and secretion of brain-derived neurotrophic factor (BDNF). Intraperitoneal injection of minocycline, a microglial inhibitor, suppressed microglial activation and reversed neurogenesis. Our data showed that sevoflurane preconditioning promoted microglial activities, created a favorable microenvironment for endogenous neurogenesis and accelerated functional reconstruction in the infarct region.
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